It is proposed to investigate further the mechanism of action of the enzymes chymotrypsin and trypsin by attempting to find indirect evidence for a tetrahedral intermediate. This will be done by comparing corresponding oxygen and sulfur esters of specific substrates. In addition we plan to investigate extremely fast systems where the rate-determining step is binding in particular to see what effect this phenomenon will have on rate constants and pH dependencies. We further propose to change trypsin to a chymotrypsin-like enzyme by chemical modification and propose to change a protein which has only a binding site into an enzyme which has both a binding site and a catalytic site. To do this we must add catalytic groups to the protein. We further intend to change more oxygen enzymes to the corresponding sulfur enzymes to understand the limitations of this transformation.